ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1375_1376TC[2] (p.Leu460fs) (rs1064793128)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485073 SCV000565011 pathogenic not provided 2017-08-30 criteria provided, single submitter clinical testing The c.1379_1380delTC variant in the FLCN gene has been reported previously in association with Birt-Hogg-Dube syndrome (Schmidt et al., 2005; Toro et al., 2008; Miura et al., 2015; Furuya et al., 2016). The deletion causes a frameshift starting with codon Leucine 460, changes this amino acid to a Glutamine residue and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Leu360GlnfsX25. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider c.1379_1380delTC to be pathogenic.
Ambry Genetics RCV000492502 SCV000580760 pathogenic Hereditary cancer-predisposing syndrome 2017-10-11 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000702300 SCV000831149 pathogenic Multiple fibrofolliculomas 2019-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu460Glnfs*25) in the FLCN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with Birt-Hogg-Dub syndrome and to segregate with disease in affected families (PMID: 15852235, 18234728, 20618353, 22441547, 26943385, 27220747, 28009417). This variant is also known as 1834delTC or 1834-5delTC in the literature. ClinVar contains an entry for this variant (Variation ID: 418213). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.

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